Publication
T cell cholesterol efflux suppresses apoptosis and senescence and increases atherosclerosis in middle aged mice
Publisher:
Springer Science and Business Media LLC
Date:
07-2022
DOI:
10.1038/S41467-022-31135-4
Abstract: Atherosclerosis is a chronic inflammatory disease driven by hypercholesterolemia. During aging, T cells accumulate cholesterol, potentially affecting inflammation. However, the effect of cholesterol efflux pathways mediated by ATP-binding cassette A1 and G1 (ABCA1/ABCG1) on T cell-dependent age-related inflammation and atherosclerosis remains poorly understood. In this study, we generate mice with T cell-specific Abca1/Abcg1 -deficiency on the low-density-lipoprotein-receptor deficient ( Ldlr −/− ) background. T cell Abca1/Abcg1 -deficiency decreases blood, lymph node, and splenic T cells, and increases T cell activation and apoptosis. T cell Abca1/Abcg1 -deficiency induces a premature T cell aging phenotype in middle-aged (12–13 months) Ldlr −/− mice, reflected by upregulation of senescence markers. Despite T cell senescence and enhanced T cell activation, T cell Abca1/Abcg1 -deficiency decreases atherosclerosis and aortic inflammation in middle-aged Ldlr −/− mice, accompanied by decreased T cells in atherosclerotic plaques. We attribute these effects to T cell apoptosis downstream of T cell activation, compromising T cell functionality. Collectively, we show that T cell cholesterol efflux pathways suppress T cell apoptosis and senescence, and induce atherosclerosis in middle-aged Ldlr −/− mice.